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PREDICTIVE AND PROGNOSTIC MARKERS IN SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

Henriksson, Eva LU (2008) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2008:84.
Abstract
Survival of patients with locally advanced head and neck squamous cell cancer(HNSCC)is poor, with an overall survival < 50%, despite diagnostic and therapeutic advances. The identification of prognostic and predictive markers could help optimizing treatment.

From 18 patients, six tumour cell lines were established and four were xenografted to nude mice. Proliferation parameters(cell doubling time, S-phase fraction), TP53- and CCND1 status were studied in relation to cisplatin response. Metabolic activity was studied by 2-deoxy-2[18F]fluoro-D-glucose(FDG) uptake.

Successful cell-line establishment was correlated to poorer survival than when cell lines failed to establish. Shorter doubling time was correlated to higher... (More)
Survival of patients with locally advanced head and neck squamous cell cancer(HNSCC)is poor, with an overall survival < 50%, despite diagnostic and therapeutic advances. The identification of prognostic and predictive markers could help optimizing treatment.

From 18 patients, six tumour cell lines were established and four were xenografted to nude mice. Proliferation parameters(cell doubling time, S-phase fraction), TP53- and CCND1 status were studied in relation to cisplatin response. Metabolic activity was studied by 2-deoxy-2[18F]fluoro-D-glucose(FDG) uptake.

Successful cell-line establishment was correlated to poorer survival than when cell lines failed to establish. Shorter doubling time was correlated to higher FDG uptake in vitro. Different bioassays were used to measure

cisplatin sensitivity in vitro. The colony forming assay was the most effective measure of cell kill.

Sequential changes in FDG uptake and in the histopathological appearance during chemotherapy

were studied. FDG uptake was correlated to amount of viable tumour cells and to tumour cell viability with a decreasing uptake over time in prenecrotic cells following treatment response. A very early transient increase in FDG uptake per cell was seen in both in vivo and in vitro studies.

Conclusion: Establishment of in vitro growth is an independent, negative prognostic factor. p53 mutation and cyclin D1 amplification predict a poor response to cisplatin. Early metabolic response is predictive of successful treatment effect. Uptake of FDG is mainly present in tumour cells with no interference from surrounding tissue. This is important when interpreting a metabolic tumour image(FDGPET scan). (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Grenman, Reidar, Dept.of Otorhinolaryngology, Head and Neck Surgery, Turku University Central Hosital, Finland
organization
publishing date
type
Thesis
publication status
published
subject
keywords
CCND1, cyclin D1, head and neck cancer, cisplatin, TP53, cell proliferation parameters, squamous cell carcinoma, predictive marker
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2008:84
pages
50 pages
publisher
Lund University
defense location
Lecturehall of the Department of Oncology, Lund University Hospital
defense date
2008-09-26 13:00
ISSN
1652-8220
ISBN
978-91-86059-37-8
language
English
LU publication?
yes
id
b600b456-dd72-4f9e-b1b8-377367b3170d (old id 1223917)
date added to LUP
2008-09-04 08:53:20
date last changed
2016-09-19 08:44:49
@phdthesis{b600b456-dd72-4f9e-b1b8-377367b3170d,
  abstract     = {Survival of patients with locally advanced head and neck squamous cell cancer(HNSCC)is poor, with an overall survival &lt; 50%, despite diagnostic and therapeutic advances. The identification of prognostic and predictive markers could help optimizing treatment.<br/><br>
From 18 patients, six tumour cell lines were established and four were xenografted to nude mice. Proliferation parameters(cell doubling time, S-phase fraction), TP53- and CCND1 status were studied in relation to cisplatin response. Metabolic activity was studied by 2-deoxy-2[18F]fluoro-D-glucose(FDG) uptake.<br/><br>
Successful cell-line establishment was correlated to poorer survival than when cell lines failed to establish. Shorter doubling time was correlated to higher FDG uptake in vitro. Different bioassays were used to measure<br/><br>
cisplatin sensitivity in vitro. The colony forming assay was the most effective measure of cell kill.<br/><br>
Sequential changes in FDG uptake and in the histopathological appearance during chemotherapy <br/><br>
were studied. FDG uptake was correlated to amount of viable tumour cells and to tumour cell viability with a decreasing uptake over time in prenecrotic cells following treatment response. A very early transient increase in FDG uptake per cell was seen in both in vivo and in vitro studies.<br/><br>
Conclusion: Establishment of in vitro growth is an independent, negative prognostic factor. p53 mutation and cyclin D1 amplification predict a poor response to cisplatin. Early metabolic response is predictive of successful treatment effect. Uptake of FDG is mainly present in tumour cells with no interference from surrounding tissue. This is important when interpreting a metabolic tumour image(FDGPET scan).},
  author       = {Henriksson, Eva},
  isbn         = {978-91-86059-37-8},
  issn         = {1652-8220},
  keyword      = {CCND1,cyclin D1,head and neck cancer,cisplatin,TP53,cell proliferation parameters,squamous cell carcinoma,predictive marker},
  language     = {eng},
  pages        = {50},
  publisher    = {Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {PREDICTIVE AND PROGNOSTIC MARKERS IN SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK},
  volume       = {2008:84},
  year         = {2008},
}